Familial congenital choanal atresia with GATA3 associated hypoparathyroidism-deafness-renal dysplasia syndrome unidentified on auditory brainstem response

Auris Nasus Larynx. 2019 Oct;46(5):808-812. doi: 10.1016/j.anl.2018.10.005. Epub 2018 Nov 2.

Abstract

Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is a rare autosomal dominant disorder primarily caused by GATA3 haploinsufficiency and is challenging to diagnose in early childhood. We report a Japanese family with HDR syndrome and congenital choanal atresia. The 6-year-old female proband was diagnosed with epilepsy at the age of three. Under carbamazepine monotherapy, the patient presented hypoparathyroidism accompanied by severe hypocalcemia. Subsequently, renal ultrasound analysis revealed bilateral multicystic dysplastic kidneys. Because she had difficulty hearing, we sequenced GATA3 and determined that she had a c.708_709insC (p.Ser237Glnfs*66) allelic variant in exon 3. As a result, we found a family of this disease. Each family member, including her grandfather, mother, and two siblings, had HDR syndrome of varying clinical penetrance. We found a craniofacial anomaly, congenital choanal atresia, which was inherited as an autosomal dominant trait. Hypocalcemia coupled with vitamin D deficiency, triggered by carbamazepine treatment, ultimately revealed the proband's childhood- onset HDR syndrome. Pure-tone audiometry revealed different severities of deafness as well as the progression of sensory hearing loss. However, auditory brainstem response for hearing screening is probably insufficient for ascertaining HDR syndrome in the early stages of life. We presented new clinical clues to diagnose the HDR syndrome.

Keywords: Congenital choanal atresia; GATA binding protein 3; Hypoparathyroidism-deafness-renal dysplasia; Sensorineural hearing loss.

MeSH terms

  • Adult
  • Anticonvulsants / adverse effects
  • Audiometry, Pure-Tone
  • Carbamazepine / adverse effects
  • Child
  • Choanal Atresia / complications
  • Choanal Atresia / diagnosis
  • Choanal Atresia / genetics*
  • Epilepsy / drug therapy
  • Evoked Potentials, Auditory, Brain Stem
  • Female
  • GATA3 Transcription Factor / genetics*
  • Grandparents
  • Haploinsufficiency
  • Hearing Loss, Sensorineural / complications
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Hypocalcemia / chemically induced
  • Hypocalcemia / etiology
  • Hypoparathyroidism / complications
  • Hypoparathyroidism / diagnosis
  • Hypoparathyroidism / genetics*
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mothers
  • Neonatal Screening
  • Nephrosis / complications
  • Nephrosis / diagnosis
  • Nephrosis / genetics*
  • Pedigree
  • Siblings
  • Tomography, X-Ray Computed
  • Vitamin D Deficiency / chemically induced

Substances

  • Anticonvulsants
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Carbamazepine

Supplementary concepts

  • Barakat syndrome